The present invention relates to the standard materials useful for the detection and measurement of immune complexes (or antigen-antibody complexes) existing in the blood, blood-plasma or other body fluids of a patient who is suffering from diseases arising from immune complexes and to the quantitative measurement of immune complexes by use of said standard material.
Immune complex diseases may be brought under two categories, i.e. such diseases resulting from endogenous autoantigen as chronic articular rheumatism, systemic lupus erythematosus (SLE), chronic glomerulonephritis, tumor, etc., and such diseases resulting from exogenous antigen as acute glomerulonephritis, leukemia, etc. The formation of immune complexes is one of the protective reactions which take place in a living body and they are ingested and destroyed by reticuloendothelial cells and other phagocyte immediately after their formation in the body of a person in normal health. Under abnormal conditions, however, where immune complexes are formed in large quantities due to continued antigenical stimulus or where they unyieldingly get beyond control of reticuloendothelial cells and phagocytes, the immune complexes remain in the blood, blood-plasma, or other body fluids to settle in the tissue of the human body and finally destruct the tissue. The determination of immune complexes in the blood, blood-plasma or body fluids is, therefore, to offer reliable information useful for making diagnosis of and trying remedies for diseases resulting from immune complexes. In view of such vital need for quantitative estimation of immune complexes existing in the blood or body fluids, various means are now put into practice, of which immunochemical assay has widely come into use because of its accurate determination and simple procedures.
In this immunochemical assay, immune complex is measured by use of a substance which is able to combine specifically with the component of immune complex, such as complement component, conglutinin (kg), anticomplementary antibody, Raji cell, rheumatoid factor (RF), and blood platelet, followed by comparison of the obtained result with the immune complex standard material of known concentration. Since it is impracticable to separate immune complexes which actually exist in the blood or body fluids for use in the assay, a similitude of immune complex which has characteristics immunologically similar to immune complex. As a similitude of immune complex to be used as a standard agent in the assay, a substance obtained by treating immunoglobulin with heat and chemicals to have it denatured and aggregated, such as aggregated human immunoglobulin (AHG) and a substance obtained by cross-linking immunoglobulin with the use of a bisudiazo compound and the like to have it denatured are presently used.
However, it is difficult to prepare these substances of good reproducibility and constant properties because of lack of uniformity in their properties including molecular weight. Moreover, they have another defect of having unsatisfactory shelf life stability which tends to form a precipitate or sediment, thus making it difficult to give an accurate concentration value when used in measurement. Since it is especially very difficult to obtain a similitude of immune complex having complement reactivity in case where human IgA is used for aggregation purpose as a standard material for use in measuring IgA immune complex, attempts have been made to have IgA and IgG aggreagatad together; however, much difficulty is still found in preparing standard agents of good uniformity and excellent reproducibility, thus constituting a barrier against an accurate measurement of IgA immune complex.